Harnessing the power of the immune system to treat chronic infectious diseases or cancer is a major goal of immunotherapy. Vaccinations (aka, active immunotherapy) are designed to activate the immune system to specifically recognize and protect against invading pathogens. For over 200 years, active immunotherapy approaches have been used to prevent numerous infectious diseases, including small pox, rabies, typhoid, cholera, plague, measles, varicella, mumps, poliomyelitis, hepatitis B and the tetanus and diphtheria toxins.
Active immunotherapy concepts are now being applied to develop therapeutic cancer vaccines with the intention of treating existing tumors or preventing tumor recurrence, as well as being applied to the treatment and prevention of chronic viral infections. However, existing active immunotherapy technology has not been successful in protecting against many of the modern vaccine targets such as HIV/AIDS, Hepatitis B and cancer. This is in part due to the inability of current vaccination technology to elicit the correct type of immune responses.
The type of immune response generated to infection or other antigenic challenges can generally be distinguished by the subset of T helper (Th) cells involved in the response. Immune responses can be broadly divided into two types: Th1 and Th2. Th1 immune activation is optimized for intracellular infections such as viruses and involves the activation of Natural Killer (NK) cells and Cytolytic T-cells (CTL) that can lyse infected cells, whereas Th2 immune responses are optimized for humoral (antibody) responses. Th1 immune activation is the most highly desired for cancer therapy and Th2 immune responses are directed more at the secretion of specific antibodies and are relatively less important for tumor therapy. Prior art vaccine compositions are specialized in eliciting Th2 or humoral immune responses, which are not effective against cancers and most viral diseases.
The use of adjuvants is a strategy for influencing the immune response to antigens in a vaccine composition. Aluminum salts, and squalene oil in water emulsion (MF59) are the most widely used adjuvants in human vaccines. These adjuvants predominantly promote Th2 humoral (antibody) responses to antigens and are effective at elevating serum antibody titers, but do not elicit significant Th1 responses or CTLs. However, vaccines against chronic infections (e.g., human immunodeficiency virus (HIV), hepatitis C virus (HCV), tuberculosis, herpes simplex virus (HSV)) and cancer cells require generation of Th1 cellular immune responses for protection and therapeutic effect.
Some experimental active immunotherapy techniques and protocols in the prior art have proven to successfully elicit Th1 responses against tumor antigens in select patients, resulting in increased frequencies of CTL immune cells in circulation that have the ability to specifically kill tumors or pathogen infected cells. However, despite the ability to elicit Th1 responses tumor escape mechanisms can overpower this immune response resulting in eventual tumor progression. Viruses have also developed a number of countermeasures to avoid immune attack and stay moving targets for the immune system.